1 Hersenen en geslachtshormonen: over neurosteroïden, seksueel gedrag en de hersencyclus.Petra De SutterUZ GentSince Prof. Van Herendael asked me to talk about three topics, I thought he would give me three quarters of an hour to talk. I will do my very best to clear the job in 15 minutes. NEXT

2 Inleiding hersenen voortplanting seksualiteitConsidering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDEvoortplantingseksualiteit

3 hersenen voortplanting seksualiteit neurosteroïden ? steroïdenConsidering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDEvoortplantingseksualiteit

4 Seksuele differentiatie en dimorfisme van de hersenenSeksualiteit en hersenenOestrogenen, humeur en cognitieConsidering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDE

5 Werking van steroïden Oestradiol:Bindt op ER-α en op ER-β (verschillende weefseldistributie, ook in de hersenen)Traag en langdurend genomisch effectKlassiek effectSnel en kortdurend non-genomisch effectSeksuele differentiatie hersenen?Plasticiteit hersenen ?T -> aromatase -> E2 (differentiatie in mannelijke richting ~ hogere dosis E2, o.a. de novo)Considering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDE

7 Werking van steroïden Oestradiol: Progesteron is ’ neurotroof ’:induceert synapsformatie,gaat de synapsdestructie oiv progesteron tegenremt apoptose en is anti-oxydansInduceert progesteron receptoren (progesteron doet E2 receptoren dalen!)ProgesteronAllopregnanolon (metaboliet en neurosteroïd): bindt centraal op GABA-A receptor (centrale inhibitie -> sedatief-hypnotisch cfr barbituraten)>< pregnenolon: GABA antagonist !Considering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDE

8 Prenatale steroïden en de hersenenSteroïdreceptoren:limbisch systeem (hypothalamus en amygdala)Regelt « overlevings » gedrag zoals honger, dorst, agressie, reproductieSexueel dimorfe hersenkernen (knaagdieren) -> hypothalamusMannetjes: A -> E2 -> mannelijk fenotypeGeen LH surge op E2 stijging, agressief seksueel gedragVrouwtjes: E2 vnl gebonden en niet voorbij bloed-hersenbarrière -> vrouwelijk fenotypeWel LH surge op E2 stijging, receptief seksueel gedragOmkeerbaar door castratie (M->V) of androgeentherapie (V->M)Considering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDE

10 Seksueel dimorfisme van de hersenenMens: dimorfisme aangetoond, bepaalde kernen groter bij mannen dan bij vrouwen, behalve bij homoseksuelen (INAH3 – 3rd interstitial nc of the anterior hypothalamus) en transseksuelen (BSTc -bed-nucleus of the stria terminalis)Mol Brain res (2003): differentiële genexpressie (50tal genen) in de hersenen bij muizen, vóór steroïd differentiatie !Considering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDE

14 steroïden en seksueel gedragKnaagdieren:perivulatoir: seksueel receptief (lordose)postovulatoir: vijandig tov mannetjesConsidering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDE

16 Hersenen en seksualiteit bij de vrouwAndrogenen: verhogen libido, seksuele fantasieën en motivatie bij de vrouw (Money 1961)Female Sexual Dysfunction: stoornissen van seksuele begeerte, opwinding, orgasme stoornissen en seksuele pijnsyndromen43% van alle vrouwenMasters/Johnson en Kaplan model = typisch mannelijk(begeerte -> opwinding -> orgasme -> resolutie)Considering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDEzelfbeeldHouding tov sexSex drivehormonenpartnerrelatie

17 Hersenen en seksualiteit bij de vrouwFemale Sexual Dysfunction: stoornissen van seksuele begeerte, opwinding, orgasme stoornissen en seksuele pijnsyndromen (International Consensus Classification System(1999))I. Sexual desire disordersA. Hypoactive sexual desire disorder (33%)B. Sexual aversion disorder (phobic)II. Sexual arousal disorder (lubrication) (20%)III.Orgasmic disorder (25%)IV. Sexual pain disorderA. DyspareuniaB. VaginismusC. Other sexual pain disorders (non-coital)(V. Sexual satisfaction disorder ? -20%)Considering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDE

23 Het CZS en coïtusPerifeer visuele, tactiele, auditieve of reukprikkelsLokaal aanraking/stimulatie genitaliasensoriële banensacrale spinale tractusautonome reflexen (secretie, spiercontracties)Centraal sensoriële cortex: bewuste perceptielimbisch systeem: plezierhypothalamus stimulatiehypofyse: FSH, LH en oxytocineConsidering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDE

24 Oxytocine, het « love hormone »- gesecreteerd door hypothalamus -> hypofyse onder invloed van diverse prikkels (cervicovaginaal, tepels)- piekt tijdens masturbatie/coïtus met orgasme- doet uterus samentrekken (semen transport) - belang tijdens de arbeid, piekt onmiddellijk postpartum (inductie van materneel gedrag)- stijgt bij prikkels vanwege de baby (geluid, zicht, gedachten) -> piekt tijdens het zuigen- parallel met oxytocine pieken ook de endorfines (pijn en plezier, bonding)- wordt uitgelokt door aanraking, knuffelen, intimiteit, bonding (ook gestimuleerd door E2: belang voor de vrouw groter dan de man?)Considering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDE

26 Het hypo-oestrogeen continuum van de vrouwelijke hersenenPMS/PMDD, postnatale depressie en perimenopause:Depressie, slaapstoornissen, irritabiliteit, angst en paniekaanvallen, geheugen- en cognitieve dysfunctie, gedaald ‘well-being’ gevoelGemeenschappelijk: oestrogeen deprivatie !E2: veroorzaakt stijging van dopamine, norepinefrine, serotonine en beta-endorfines, vermindert MAO activiteitE2 stimuleert het NN-methyl-D-aspartaat (NMDA) netwerk: excitatie (>< GABAa balanceert het NMDA netwerk): bvb meer epilepsie preovulatoir, ‘restless legs’ syndroomProgesteron: veroorzaakt daling van amines, stijging van MAO activiteit < daling E2 receptoren? -> ‘mood changes’Neurosteroïden: de novo gesynthetiseerd uit cholesterol in de hersenen ~ geen verband met serumspiegelsConsidering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDE

28 Geheugen, cognitie en oestrogenenHippocampus: centrum van korte termijn geheugen en cognitie < wordt door E2 gemodelleerdE2 doet acetylcholine en lokale doorbloeding stijgen waardoor imprinting van nieuwe gegevens beter gebeurtE2 substitutie verbetert korte termijn geheugen en cognitie, beschermt tegen Alzheimer (primaire, zeker geen secundaire preventie) ???WHI-Memory Study (JAMA mei 2003):Cognitieve functie slechter bij 6.7% E+P behandelde vrouwenVs 4.8% placebo-> in vitro is progesteron neuroprotectief (potentialiseert E2), doch MPA NIET (eerder antagonist)!Belang van SERMs?Considering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDE

29 Dank U voor Uw aandacht !Considering a presentation on alternative techniques for evaluation of abnormal uterine bleeding, the first question that came to my mind was : why? Why should we still use other investigational methods when we have such a powerful tool as hysteroscopy? So why not use it as a primary investigational tool?We already focused yesterday on the costs of hysteroscopy, which are considerably higher than for example ultrasound.Secondly, since in more than half of the cases of abnormal bleeding it is dysfunctional in cause, the « return » on surgical intervention will be much lower than 50%, so that preliminary screening is very appealing.Furthermore it remains an invasive procedure, which can cause some discomfort for the patients and can induce some complications. Of course we all know that these are rare in experienced hands, and I think that this is the main disadvantage of hysterocopy : it takes quite some experience. First, I would like to adress the case of transvaginal sonography.NEXT SLIDE

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